Perioperative Antihypertensive Treatment in Patients With Spontaneous Intracerebral Hemorrhage
Background—Studies on antihypertensive treatment for surgical patients with spontaneous intracerebral hemorrhage are insufficient. This pilot study was conducted to investigate the safety of the perioperative intensive blood pressure lowering in surgical patients with spontaneous intracerebral hemorrhage.
Methods—This study was a prospective, parallel, randomized, assessor-blinded trial. Patients allocated to the intensive group received perioperative intensive antihypertensive treatment aiming to achieve a target systolic blood pressure between 120 and 140 mm Hg, whereas the patients in the conservative group received conservative treatment aiming to achieve a target systolic blood pressure between 140 and 180 mm Hg for 7 days. The primary outcome was the rate of rehemorrhage at 7 days after surgery.
Results—Rehemorrhage was noted in 11 patients (11%) in the intensive group and 14 (14%) in the conservative group (P=0.689). There was no significant difference in mortality at 7 days (4.0% versus 10.0%; P=0.164), 30 days (10.4% versus 17.2%; P=0.247), and 90 days (13.5% versus 18.2%; P=0.490) between the 2 groups.
Conclusions—Perioperative intensive blood pressure lowering was not associated with a reduced incidence of rehemorrhage, death, or other serious adverse events.
Clinical Trial Registration—URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR-TRC-13004304.
- antihypertensive agents
- blood pressure
- cerebral hemorrhage
- prospective studies
- randomized controlled trial
Previous studies have shown that blood pressure (BP) elevation is common after spontaneous intracerebral hemorrhage (sICH), and early-elevated BP is related to hematoma growth and poor functional outcome.1,2 The results of 4 randomized controlled trials suggest that early intensive BP lowering is safe for patients with sICH.3–6 However, patients undergoing surgical evacuation were not evaluated in these randomized controlled trials.
The key aim of the PATICH study (Perioperative Antihypertensive Treatment in Patients With Spontaneous Intracerebral Hemorrhage) was to evaluate the safety of intensive antihypertensive treatment for patients with sICH who underwent surgical hematoma evacuation. Full details of the study design are outlined elsewhere.7 This study is registered with www.chictr.org (ChiCTR-TRC-13004304). In brief, this was a single-center, prospective, open, blinded outcome-assessed, randomized trial. Eligible patients were aged ≥ 18 years, had computed tomography- or magnetic resonance imaging–confirmed sICH with elevated systolic BP (SBP) between 150 and 220 mm Hg (at least 2 measurements) and were able to receive surgery within 24 hours after ictus. Patients were excluded for having a definite indication or contraindications to antihypertensives, secondary intracerebral hemorrhage, a Glasgow Coma Scale score between 3 and 5, a definite contraindication to operation, advanced dementia or disability before ICH onset, or comorbidities that would interfere with the outcome assessment and follow-up. Given that both the patients and doctors could not be blinded in this trial, the assessor was blinded. The postoperative rehemorrhage rate was reported to be ≈23% (10%–36%).8–10 An observational study and our retrospective clinical data showed that the rehemorrhage rate for patients with perioperative elevated BP was ≈4× higher than those with normal BP.11 Assumptions were made that intensive BP lowering could reduce the rehemorrhage rate from 23% to 6%, and a sample size of 90 patients in each group would be required to achieve a significance level of 5% (2 sided) and a power of 90%. In consideration of a 10% loss, the sample size was increased to 200 (100 in each arm).
Eligible patients were allocated to an intensive treatment or conservative treatment group randomly by the method of minimization within 1 hour after admission. A special researcher conducted the randomization of patients using the Minimpy program (version 0.3) with stratified factors including age, time since ICH onset, time to surgery, admission Glasgow Coma Scale, and location of hematomas. In the intensive group, the target SBP at the end of the first hour after randomization was between 140 and 160 mm Hg and that at the time of surgery was between 120 and 140 mm Hg using intravenous drugs. After the operation, the antihypertensive treatment began when the SBP became elevated to >140 mm Hg. The target postoperative SBP was between 120 and 140 mm Hg. The target SBP was maintained for 7 days after randomization or until hospital discharge within 7 days. The oral antihypertensive drugs were administered as soon as possible. In the conservative group, the target perioperative SBP was between 140 and 180 mm Hg. The intraoperative SBP was maintained at between 90 and 140 mm Hg by anesthesiologists for both groups.
In this study, the operations were conducted by well-trained neurosurgeons, and guideline-recommended medical treatments were performed during hospitalization.
The primary outcome of this study was the incidence of rehemorrhage within 7 days after randomization. The rehemorrhage was defined as a greater postoperative hematoma volume, a difference of ≤5 mL between the pre- and postoperative hematoma volumes8,9 or a difference of ≥5 mL in hematoma volumes between the first postoperative computed tomography and the subsequent computed tomography. Secondary outcomes included neurological function at 90 days; 7-, 30-, and 90-day mortality; health-related quality of life at 90 days; and incidence of complications.
Methods of computed tomographic scans, data collection, follow-up, and statistical analysis are available in the online-only Data Supplement.
The study included 201 patients from the period between September 2013 to September 2014 (Figure I in the online-only Data Supplement). The baseline characteristics of the patients were well matched (Table 1). The patients in the intensive group received significantly more antihypertensives (Table I in the online-only Data Supplement). In this study, 193 patients were treated to target SBP before surgery, whereas 191 were treated to target SBP within 1 hour after surgery. The mean SBPs in both groups were managed at the target level after randomization (Figure II in the online-only Data Supplement).
In this study, 11 patients (11%) in the intensive treatment group and 14 (14%) in the conservative treatment group had rehemorrhage within 7 days after randomization (P=0.689). The mean rehemorrhage volumes in the intensive and conservative groups were 34 and 31 mL, respectively (P=0.405). Subgroup analyses results are listed in Table II (online-only Data Supplement). No heterogeneity was found.
Twenty-seven of the 210 patients died within 30 days after randomization and 31 died within 3 months. The mortality in the intensive group was lower than that in the conservative group at each time point (Table 2). For complications, the incidence of ischemia, vascular events, and acute renal failure was similar between the 2 groups (18.0% versus 13.9%, P=0.423; 0.0% versus 2.0%, P=0.498; 1.0% versus 1.0%, P=1.000). There was no significant difference in the functional outcome or health-related quality of life (Table III in the online-only Data Supplement).
The results of this pilot study show that early perioperative intensive BP lowering did not seem to be associated with serious adverse events in patients with large hematomas who underwent surgical evacuation.
In contrast to the procedure in previous randomized controlled trials, we used rehemorrhage as the primary outcome. Rehemorrhage is the most severe postoperative complication for patients with sICH. It has been reported that the incidence of rehemorrhage is 10% to 36% after craniotomy for hematoma evacuation in patients with sICH, and only a few rehemorrhage patients have favorable outcomes.8–10 Previous studies have shown that the surgical procedure, time interval from ictus to surgery and level of BP are correlated with rehemorrhage.11 In the present study, the time interval from ictus to surgery was between 4 and 24 hours, and the overall incidence of rehemorrhage was 12%. The rate of rehemorrhage was similar to previous reports. However, we did not detect any significant difference in the incidence of rehemorrhage between the intensive and conservative antihypertensive treatments. The results of our study suggest that elevated BP might not be the main critical risk factor for rehemorrhage. Although patients enrolled in this study had a larger hematoma and worse neurological function at admission compared with other trials, they had similar 90-day mortality rates.4,6 In addition, the occurrence of severe complications was also similar to published data. Consistent with previous studies, the findings of the present study confirm that intensive BP lowering does not increase mortality or the incidence of severe complications in sICH patients who have undergone surgical evacuation.
Perioperative intensive BP lowering was not associated with an increased incidence of rehemorrhage, death, or other serious adverse events.
We sincerely thank the patients for giving their informed consent to participate and everyone who made this research possible.
Sources of Funding
This study was supported by The National Key Technology R&D Program for the 12th Five-year Plan of P.R. China (no. 2011BAI08B05).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.116.014285/-/DC1.
- Received June 2, 2016.
- Revision received September 10, 2016.
- Accepted October 18, 2016.
- © 2016 American Heart Association, Inc.
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